tbuckley/cabot-search huggingface dataset:
Prevalence of <i>EGFR</i> mutations in patients with resected stage I-III non-squamous NSCLC: Results from the EARLY-EGFR study.
Authors: Ross A. Soo, Thanyanan Reungwetwattana, Herman Andres Perroud, Ullas Batra, Saadettin Kilickap, Luis Fernando Tejado Gallegos, Natalia Donner, Mohamed Alsayed, Reto Huggenberger, Tu Van Dao
Journal: Journal of Clinical Oncology (2023)

8531 Background: The prevalence of EGFR mutations ( EGFRm) in resected stage I-III NSCLC remains controversial as prior research studies were retrospective in nature. EARLY-EGFR is the first prospective, international study to determine the prevalence of EGFRm and treatment patterns in patients (pts) with early-stage NSCLC. Methods: EARLY-EGFR (NCT04742192), a non-interventional real-world study, captured data on EGFRm status, treatment patterns, demographic, clinical and pathological characteristics in consecutively enrolled pts with surgically resected stage IA-IIIB (AJCC 8 th ) non-squamous NSCLC (Mar 2021 – Oct 2022). The primary endpoint was prevalence of EGFRm and secondary endpoints included prevalence of EGFRm subtypes and treatment patterns. Results: Of 601 pts (median [range] age: 62 [30-86] yrs) enrolled at 33 centers across Middle East and Africa (n=16), Latin America (n=80), and Asia (n=505), 317 (52.7%) were females, 354 (58.9%) were never smokers. The majority had stage IA-IB NSCLC (64.1%) involving right lung (62.9%), no nodal involvement (81.5%), T1a-T2b tumor (82.7%), adenocarcinoma histology (98.7%), and 105/420 (25.0%) tumors were poorly differentiated. About 23.3% (130/559) were diagnosed through a screening program; 60/539 (11.1%) reported family history of lung cancer. The overall prevalence of EGFRm was 50.7% (300/592). Exon-19 deletions accounted for 50.3%, L858R mutations for 35.7%, and compound mutations for 2.3% of mutations. EGFRm tumors were found to be PD-L1 positive in 38.5% of cases (15/39). Women had higher EGFRm rate than men (63.6% vs 36.2%). Compared with EGFR wild type (wt), pts with EGFRm were more likely to be never smokers (39.5% vs 60.5%) and have stage I/II NSCLC (46.5% vs 53.5%) (Table). Of 216 stage II/III NSCLC pts, only 51.4% received systemic adjuvant therapy. Significantly higher EGFRm rates in stages I and II than in stage III NSCLC (p&lt;0.001 and p=0.050) were found, while no significant difference was found between stages I and II NSCLC (p=0.158). Conclusions: In this first prospective, real-world study of EGFRm prevalence in resected NSCLC, stage III and smoking were independent predictors associated with decreased odds of EGFRm. The results highlight the need to adhere to ASCO adjuvant chemotherapy guidelines, as only half of stage II/III NSCLC pts received adjuvant systemic therapy. Clinical trial information: NCT04742192 . [Table: see text]
Myeloablative fractionated busulfan-based conditioning regimen in patients with AML and MDS: Results of a randomized clinical trial comparing 2 fractionation schedules.
Authors: Uday R. Popat, Konstantinos Lontos, Roland L. Bassett, Amin Majid Alousi, Gheath Alatrash, Qaiser Bashir, Chitra M. Hosing, Jin Seon Im, Partow Kebriaei, David Marin, Rohtesh S. Mehta, Yago Nieto, Betul Oran, Amanda Leigh Olson, Muzaffar H. Qazilbash, Jeremy L Ramdial, Samer Ali Srour, Elizabeth J. Shpall, Richard E. Champlin, Borje S Andersson
Journal: Journal of Clinical Oncology (2023)

7051 Background: Hematopoietic stem cell transplantation (HSCT) cures leukemias, but comes at a cost of higher toxicity and non-relapse mortality (NRM). We previously showed that fractionating the busulfan (Bu) dose and starting it on day -13 instead of day -6, leads to lower toxicity and permits delivery of a myeloablative regimen, even to older patients. We designed a single institution randomized trial to validate the concept of fractionation and to test the hypothesis that further fractionation by starting chemotherapy on day -20 further reduces toxicity and lowers NRM without increasing relapse risk. Methods: Patients with AML or MDS, 18 to 70 years old, with a matched related or unrelated donor were eligible if they had adequate organ function. Patients were randomized to one of two arms: The shorter arm consisted of outpatient Bu 80mg/m 2 on days -13 and -12, while the longer arm consisted of outpatient Bu 80mg/m 2 on days -20 and -13. The rest of the regimen and GVHD prophylaxis were similar in both arms: On days -6 to -3, fludarabine 10mg/m 2 , cladribine 10mg/m 2 and Bu dosed to achieve total Bu exposure of 20,000 ± 12% µMol-min for the whole course, including outpatient doses. Additionally, the last 33 patients received venetoclax from days -22 to -3 in both arms. The GVHD prophylaxis was tacrolimus and mini-methotrexate in the first 29 patients and tacrolimus and cyclophosphamide in the remainder. The only difference between the two arms was if busulfan was started on day -20 or not. Results: A total of 116 patients were randomized, 59 to the shorter day -13 arm and 57 to the longer day -20 arm. Median age was 59 in the day -13 arm and 57 in the -20 arm. 70.7% had AML. 41.4% were transplanted in first complete remission. The characteristics of the two groups were well-balanced. The median follow-up in the 67 surviving patients was 48.9 months. More patients in the day -13 group experienced grade ≥3 toxicities than in the day -20 group (93.2% vs. 73.7%, p = 0.005). The difference in toxicity led to a reduction of the 3-year NRM (19% vs. 7%, p = 0.067). There was no difference in relapse rate (p = 0.99) (Table). Conclusions: Further fractionating busulfan and moving just one dose of busulfan 1 week earlier reduces toxicities and may lower NRM, without increasing relapse rate. Clinical trial information: NCT02250937 . [Table: see text]
Radiation-sensitive genetic prognostic model to identify individuals at risk for radiation resistance in head and neck squamous cell carcinoma.
Authors: Peimeng You, Qiaxuan Li, HaiYu Zhou
Journal: Journal of Clinical Oncology (2023)

e18042 Background: The advantages of radiotherapy for head and neck squamous cell carcinoma (HNSCC) depend on the radiation sensitivity of the patient. Here, we established and verified radiological factor-related gene signature and built a prognostic risk model to predict whether radiotherapy would be beneficial. Methods: Data from The Cancer Genome Atlas, Gene Expression Omnibus, and RadAtlas databases were subjected to LASSO regression, univariate COX regression, and multivariate COX regression analyses to integrate genomic and clinical information from patients with HNSCC. HNSCC radiation-related prognostic genes were identified, and patients classified into high- and low-risk groups, based on risk scores. Variations in radiation sensitivity according to immunological microenvironment, functional pathways, and immunotherapy response were investigated. Results: We built a clinical risk prediction model comprising a 15-genes signature and used it to divide patients into two groups based on their susceptibility to radiation: radiation-sensitive and radiation-resistant. Overall survival was significantly greater in the radiation-sensitive than the radiation-resistant group. Further, our model was an independent predictor of radiotherapy response, outperforming other clinical parameters, and could be combined with tumor mutational burden, to identify the target population with good predictive value for prognosis at 1, 2, and 3 years. Additionally, the radiation-resistant group was more vulnerable to low levels of immune infiltration, which are significantly associated with DNA damage repair, hypoxia, and cell cycle regulation. Tumor Immune Dysfunction and Exclusion scores also suggested that the resistant group would respond less favorably to immunotherapy. Conclusions: Our prognostic model based on a radiation-related gene signature has potential for application as a tool for risk stratification of radiation therapy for patients with HNSCC, helping to identify candidates for radiation therapy and overcome radiation resistance.
Incidence, landscape and survival outcome of de novo malignancy after double lung transplantation.
Authors: Liam Il-Young Chung, Jeeyeon Lee, Won Jun Yang, Hye Sung Kim, Yunjoo Lee, Jisang Yu, Ankit Bharat, Young Kwang Chae
Journal: Journal of Clinical Oncology (2023)

10574 Background: Organ transplant recipients are at greater risk of developing malignancies due to their immunosuppressive management. However, the incidence of post-transplant malignancy after double lung transplantation (DLT) has not been studied. This study investigated the incidence, trends, and most common types of post-transplant malignancy following DLT. Methods: Data extracted from the Organ Procurement Transplantation Network (OPTN) registry after DLT for non-cancerous disease. We evaluated the incidence of post-transplant malignancy, and assessed the annual and cumulative risk of each malignancy after DLT. And the overall survival (OS) of recipients with or without post-transplant malignancy was analyzed by Kaplan-Meire survival method. Results: A total of 23,935 cases were identified and analyzed from the OPTN database (13,768; 57.5% male, 10,167; 42.5% female). 5,629 cases (23.5%) were found to have post-transplant malignancy and 18,306 cases (76.5%) had no post-transplant malignancy. Among patients with post-transplant malignancy 3,785 (67.2%) were male and 1844 (32.8%) were female. Those with post-transplant malignancy had a longer OS compared to those without post-transplant malignancy (P &lt; 0.001). While the median OS was 97.2 months and 5-year survival rate was 83.6% in recipients with post-transplant malignancy, the median OS was 36.7 months and 5-year survival rate was 67.3% in For those without post-transplant malignancy. The risk for post-transplant malignancy was greatest during the first 3-5 years post-transplantation. The most common types of post-transplant malignancies were squamous cell skin cancer (n = 2711, 48.2%), basal cell skin cancer (n = 965, 17.1%), lymphoma (n = 570, 10.1%), lung cancer (n = 187, 3.3%), colorectal cancer (n = 184, 3.3%). Conclusions: The lifetime incidence of post-transplant malignancy following DLT was identified to be 20.1% and those with post-transplant malignancy had a longer OS compared to those without post-transplant malignancy. Further studies are needed to investigate the underlying mechanism for the increased risk of malignancy following DLT and its association with OS.
Validation of a breast cancer polygenic risk score in 15,490 Brazilians using exome sequencing.
Authors: Flavia Eichemberger Rius, Rodrigo Santa Cruz Guindalini, Danilo Viana, Júlia Salomão, Laila Gallo, Claudia Bertolacini, Renata Mendes de Freitas, Lucas Taniguti, Danilo Imparato, Yonglan Zheng, Dezheng Huo, Olufunmilayo I. Olopade, David Schlesinger
Journal: Journal of Clinical Oncology (2023)

10631 Background: Brazil has a highly admixed population with significant Southern European, African and Native American genetic ancestries. Approximately 75% of the population has two or more continental ancestries. Therefore, breast cancer polygenic risk scores (PRS) developed in predominantly European populations requires validation in the Brazilian population. Compared with genotyping arrays and whole genome sequencing, affordable and scalable whole exome sequencing (WES) allows genotyping of both rare and common variants in the targeted regions and imputation of common variants not directly captured. In this study we validate a previously developed 3820-variant PRS using WES in 15,490 Brazilians. Methods: The cohort consisted of 6,362 women with a history of breast cancer (mean age 49.6, stddev 11.6) and 9,128 unphenotyped adults as controls (mean age 41.6, stddev 13.3). WES were performed on germline DNA and variants were called and curated. Imputation was done using the 1000 Genomes Phase 3 reference panel for variants falling outside the WES captured regions. After excluding subjects with known pathogenic or likely pathogenic variants in BRCA1, BRCA2, PALB2, PTEN, or TP53, and first or second-degree relatives of the probands, 14,577 individuals remained in the final analysis (5,730 cases and 8,847 controls). We restricted PRS calculation to 2,893 of the original 3,820 variants with an estimated global imputation accuracy of 96%. Odds ratios (OR) were adjusted using the top 10 principal components. Results: The breast cancer PRS showed a highly significant correlation with cancer risk (p-value = 7.1e-81, OR = 1.43, 95% confidence interval (CI) = 1.38-1.48 per PRS standard deviation). Compared with women in the middle deciles, those in the highest 10% had an OR of 1.93, while those in the lowest 10% had an OR of 0.52 (Table). Conclusions: In this study we show that WES can capture 76% of the variants included in a previously developed and validated breast cancer PRS, and the calculated PRS is correlated with breast cancer risk in the admixed Brazilian population. This opens the door for clinical studies into the application of PRS in Brazil, particularly in women without mutations in breast cancer high-penetrance genes. In addition, our WES-based PRS strategy can be quickly, affordably, and seamlessly adopted by labs that already offer Hereditary Breast Cancer panels that use WES as a backbone. [Table: see text]
Immunotherapy and radiotherapy in metastatic uveal melanoma: Results from a single institute study.
Authors: Jian Guan, Bin S. Teh, Amy Schefler, Eric Bernicker
Journal: Journal of Clinical Oncology (2023)

e21507 Background: Metastatic uveal melanoma carries a poor prognosis, especially for patients who are not eligible for Tebentafusp. Unlike cutaneous melanoma, checkpoint inhibitors have limited effect on uveal melanoma. The observation of Abscopal effect has inspired this study of adding radiotherapy to boost the efficacy of immunotherapy. Methods: We performed a retrospective study in Houston Methodist Hospital to evaluate the efficacy of combining immunotherapy with radiotherapy including either SBRT or Y-90 treatment. Clinical outcomes were determined by assessing best overall response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), progression-free survival(PFS) and overall survival. Results: A total of 8 patients were included for this study, among which one patient had previously progressed on immunotherapy. The median follow-up period was 19 months. The best overall response rate (ORR) and disease control rate (DCR) were 25% and 75% in patients received dual-modality combination treatment (including one complete response and one partial response). The PFS and overall survival in dual-modality combination treatment group were 5.4 months (95% CI, 1.1 to 14.9 months) and 18.7 month (95% CI, 11.1 to 23.9 months), respectively. Fifty percent of patients experienced grade 3-4 treatment-related adverse events. Conclusions: The combination of radiotherapy and immunotherapy is active in metastatic uveal melanoma with sustained response in selected patients. A randomized prospective trial may be required to confirm the benefits of dual-modality combination treatment.[Table: see text]
PEMBROCABOSARC: Combination of pembrolizumab and cabozantinib in patients with advanced sarcomas.
Authors: Sabrina Sellan-Albert, Maud Toulmonde, Mariella Spalato, Francois Bertucci, Emmanuelle Bompas, Isabelle Desmoulins, Florence Duffaud, Sophie Cousin, Celine Auzanneau, Barbara Lortal, Marina Pulido, François Le Loarer, Antoine Italiano
Journal: Journal of Clinical Oncology (2023)

TPS11586 Background: Despite optimal treatment, up to 40% of patients with sarcomas will develop locoregional and/or distant relapse and median survival in this setting is less than two years. There are very few options in the treatment of undifferentiated pleomorphic sarcomas whereas there is no specific treatment regimen established for recurrent osteosarcoma (OSS) and Ewing sarcoma (ES). Innovative strategies are therefore urgently needed in these settings. In preclinical studies, while immune checkpoint inhibitors were insufficient in controlling tumour growth, combining them with M2 macrophage or angiogenesis targeting resulted in superior tumour control (Mao et al, Clin Cancer Res 2016; Zhu et al, Cancer Res 2014). Combining both antiangiogenic and MET inhibition properties, cabozantinib has shown both preclinical and clinical activity, notably in osteosarcoma and Ewing sarcoma (Italiano et al. ESMO 2018). Interestingly, cabozantinib has also recently been shown to trigger an innate immune response in a preclinical model (Patnaik et al, Cancer Discov 2017). Altogether, these findings pave the way for studies assessing the impact of targeting angiogenesis, MET and immune response in soft-tissue and bone sarcomas. Methods: PEMBROCABOSARC (NCT05182164) is a multi-stratum, three single-arm phase 2, multicenter, open-label study investigating pembrolizumab combined with cabozantinib in patients with advanced selected sarcomas: undifferentiated pleomorphic sarcoma (stratum 1), osteosarcoma (stratum 2), Ewing sarcoma (stratum 3). Strata 1 and 2 will enroll ~32 patients and stratum 3 ~55 patients, respectively. Each stratum phase II will be conducted using a Simon's optimal two-stage design. Eligible and consented patients must be ECOG PS 0–1, have measurable and progressive disease according to RECIST 1.1 and have received less than 3 previous lines of systemic therapy for advanced disease and consent also to baseline and per treatment biopsies. Cabozantinib will be administered orally, once daily at a fixed dose of 40 mg, continuously. Pembrolizumab will be administered by intravenous infusion every 3 weeks on Day 1 of each cycle, at a fixed dose of 200 mg. Both treatments will start on Day 1 (of cycle 1). The primary endpoint is 6-months non progression rate as per RECIST 1.1. Secondary endpoints include adverse events (AEs)/serious AEs, best overall response, and progression-free survival. Pharmacodynamic and other biomarkers will be explored on blood and tumor tissue. The first patient received study drug on May, 31, 2022; 8 of planned 119 patients have been enrolled and 5 sites across France among the planned 10, are currently enrolling patients. Clinical trial information: NCT05182164 .
Standardization of pregnancy screening prior to chemotherapy: A quality improvement project.
Authors: Nirja Shah, Amy Iarrobino Laughlin, Terra Warner
Journal: Journal of Clinical Oncology (2023)

e18702 Background: Administering chemotherapy during pregnancy is considered a serious adverse event, especially during the first trimester. NCCN and QOPI Certification program standards require assessing and documenting pregnancy status for women of childbearing age before first administration of a new chemotherapy regimen. However, guidelines and policies lack standardization on patient selection. We aimed to understand and address barriers to pregnancy testing prior to initiation of chemotherapy at a large regional cancer center. Methods: An institutional guideline was developed recommending a qualitative serum beta hCG test prior to each chemotherapy cycle (≥21 days apart) for females ≤ 55 years with an intact uterus and ovaries who are not postmenopausal. A retrospective chart review between 1/2022 and 6/2022 using systematic sampling and the above algorithm revealed a baseline compliance of 17% (5/30) of patients undergoing a pregnancy test within 7 days of starting chemotherapy. In an effort to improve compliance, the guideline and educational email was sent out 08/2022 to medical oncologists, nurse educators, nurse navigators, and pharmacists. An automated nudge in the electronic health record (Epic) was added to prompt guideline concordant pregnancy testing at the time of chemotherapy treatment plan ordering. Assessments were conducted at the end of each month by systematic sampling of 20 eligible patients. Compliance was determined according to institutional guideline. Results: Among 20 assessed eligible patients per month, an average of 15.75 pregnancy tests were administered, an increase from baseline 17% compliance to 76% sustained over a 5 month period. Of the 100 cases abstracted, no pregnancies were detected. Conclusions: Electronic health record nudge in conjunction with institutional guideline and education, led to an increase in appropriate pregnancy testing prior to initiation of chemotherapy. This approach demonstrates feasibility of achieving NCCN and QOPI standards while tailoring the intervention to patients of childbearing potential. [Table: see text]
The FARGO study: Frailty assessment for risk prediction in gynecologic oncology.
Authors: Julie My Van Nguyen, Danielle Vicus, Liat Frida Hogen, Tiffany Zigras, Yetiani Roldanbenitez, Maura Marcucci
Journal: Journal of Clinical Oncology (2023)

TPS12137 Background: Little is known about how to best predict postoperative outcomes and chemotherapy tolerance in an increasingly aging and complex gynecologic oncology (GO) population. Frailty is a multidimensional age-related and disease-related state of vulnerability to stressors due to reduced capacity of different physiological systems. Resource limitations are a barrier to routine adoption of frailty assessments through comprehensive clinical evaluations in daily practice. This highlights the relevance of studying potential biomarkers of frailty, which could complement or replace clinical assessments. Frailty has been associated with worse perioperative and oncologic outcomes in many subspecialties, however the literature in patients with gynecologic malignancies is very limited. Methods: The FARGO study is a multi-centre prospective cohort study of 280 patients aged ≥55 years-old undergoing surgery, with or without chemotherapy for a suspected or confirmed gynecologic malignancy. Patient recruitment will occur over 13 months. The over-arching goal is to evaluate the predictive value of frailty assessments in predicting surgical and chemotherapy outcomes. The two primary objectives are: 1) To evaluate the predictive value of preoperative frailty assessment based on the Frailty Phenotype (FP), compared to a perioperative cardiovascular risk assessment, in predicting the composite of all-cause death or new disability at 6 months after surgery 2) To create of a biobank to explore possible biomarkers of frailty, including mitochondrial DNA levels. Secondary objectives include to evaluate the predictive value of clinical and biomarker frailty assessment for 30-day postoperative complications, for chemotherapy tolerance and 1-year recurrence-free survival. Patients will undergo frailty and cardiovascular risk assessment prior to surgery and/or neoadjuvant chemotherapy. A trained clinical research assistant will measure frailty based on the clinical frailty scale (CFS) and the FP. The cardiovascular risk calculation will be based on the preoperative Revised Cardiac Risk Index, age, and occurrence of myocardial injury after non-cardiac surgery (MINS). Research personnel blinded to the frailty and cardiovascular risk assessment will evaluate study outcomes including death, disability, and clinical events at 30 days, 6 months, and 12 months after surgery. Disability will be measured with the WHODAS 2.0 (World Health Organization Disability Assessment Schedule), a validated patient-reported outcome measure. Pre-specified blood biomarkers will be measured. Our study emphasizes patient-centered outcomes (i.e. loss of independence, short and long-term disability) and system-level outcomes. Our findings may have important implications to assist in risk stratification and planning for oncologic treatments and perioperative care needs. Clinical trial information: will be added later .